Attending Version

Vasculitis Module

Created by Dr. Arthur Bankhurst

Objectives for presentation and differential diagnosis of vasculitis:

  1. To learn the spectrum of vasculitis. Certain vasculitides tend to involve certain size blood vessels.
  2. To learn how the presentation can alert one to a diagnosis of vasculitis (and type of vasculitis).
  3. To learn what non-vasculitic disease can mimic vasculitis.
  4. To prove the diagnosis of vasculitis.
  5. To learn some of the criteria for the diagnosis of specific types of vasculitis.

References:

  1. Small Vessel Vasculitis, Jennette. J, et al, NEJM 337, 1512-1523 (1997)
  2. The Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis, Jeo. P, et al, Am J Med, 117, 39-50 (2004)

Case Presentation:

A 32 year old woman comes in to the urgent care clinic on a Friday morning with an intermittent skin rash over the legs for 2 months. Lesions are not painful and resolve with minimal discoloration. PMH is positive for chronic sinusitis requiring intermittent antibiotics. ROS is negative except for a 15 pound weight loss x2 months.

  • Objective Findings
  • Non-ulcerating purpura over the lower extremities, otherwise non-remarkable.
  • Action
  • You order a chest x-ray, CBC, urinalysis, ESR and metabolic panel and schedule a follow for next Tuesday.
  • Follow up
  • You receive the following results in the afternoon:
  • Hb 8.9, ESR 115, Creatinine 1.6, UA=20-30 RBC with 3+ protein and no casts, chest x-ray = multiple infiltrates
  • What should get done now?

a)Order an ANA, ANCA, and anti-DNA to be drawn Tuesday?

b)Admit to the hospital?

c)Schedule a rheumatology consult for Monday?

d)Call in prescription for prednisone at 40 mg bid until seen on Tuesday?

Answer: b. Admit to the hospital

This patient has significant organ dysfunction of unknown duration and suspected vasculitis.

  • Evaluate immediately.
  • Therapy will depend on obtaining a specific diagnosis. Patients can deteriorate suddenly.

Board Questions:

  1. A 17 year old woman presents with hypertension, asymmetric BPs, and angina. What are the studies to be obtained?
  1. ANCA
  2. ANA
  3. ESR, C3, C4
  4. Angiography

Answer: iv. Angiography

Angiography with intravascular pressure of aorta and primary branches. Findings: LeftSC stenosis, right renal artery stenosis, stenosis of coronary arteries.

Diagnosis: Takayasu’s

  1. A 51 year old man presents with 3 month history of fever, chills, night sweats and malaise. New onset palpable purpura on legs. Biopsy showed leukoclastic (hypersensitivity) vasculitis. Treatment with 60 mg prednisone resulted in improvement. What would you do next?
  1. Add cyclosphosphomide
  2. Add Methotrexate
  3. Add plasmapheresis
  4. Increase corticosteroids
  5. Consider additional diagnoses

Answer:v. Consider additional diagnoses

CT of abdomen showed lymphadenopathy, hepatosplenomegaly; subsequent lymph node biopsy performed.

Diagnosis: Small cell lymphoma

Objective I – The Spectrum of Vasculitis

Classification based on the size of predominant blood vessels involved

I. Primary Vasculitides

Predominantly large-vessel vasculitides (aorta, artery, occasionally arterioles)

Takayasu’s arteries

Giant cell arteries

Bechet’s disease

Predominantly medium-vessel vasculitides

Polyarteritis

Cutaneous polyarteritis

Buerger’s disease

Kawasaki’s disease

Primary angitis of the central nervous system

Predominantly small vessel vaculitides *

(arterioles, venules, occasionally veins and arteries)

Goodpasture syndrome

Churg-Strauss syndrome**

Microscopic polyangitis**

Wegener’s granulomatosis**

Cutaneous leukocytoclastic vasculitis (hypersensitivity vasculitis)

Henoch – Schonlein purpura

Essential cryoglobulinemia

Hypocomplementemicurticarial vasculitis

Renal – limited or pulmonary-renal vasculitis**

II. Secondary Forms of Vasculitis

Connective Tissue disease (RA, SLE, Sjogren’s, Inflammmatory Myopathic)

Inflammatory bowel disease

Paraneoplastic

Infection

Drug-induced vasculitis

* Small vessel vasculitis is defined as a vasculitis that affects vessels smaller than arteries, such as arterioles, venules, and capillaries. It is important to note that small vessel vasculitis sometimes affects arteries and the vascular distribution overlaps that of the medium-sized and large vessel vasculitis.

** Associated with ANCA.

Objective 2 – The Feature on Presentation Which Should Alert One to the Possibility of Vasculitis

Typical Clinical Manifestations of Large, Medium, and Small Vessel Involvement *

Large -Limb claudication

Asymmetric blood pressure

Absence of pulses

Bruits

Aortic dilatation

Medium - Cutaneous nodules

Ulcers

Livedo reticularis

Digital gangrene

Mononeuritis multiplex

Microaneurysms

Small - Purpura

Vesiculobullous lesions

Glomerulonephritis

Alveolar hemorrhage

Cutaneous extravascular necrotizing granulomas

Splinter hemorrhages

Uveitis/episcleritis/scleritis

Common Fever

to allWeight loss

Malaise

Arthralgias and arthritis

* Remember – features that greatly enhance the possibility of vasculitis: glomerulonephritis, palpable purpura, peripheral neuropathy, ischemia in young patients (claudication, MI, TIA, hypertension), heart murmur, history of high risk sex activity, history of prominent liver abnormalities.

Objective 3 – What diseases can mimic vasculitis?

Sepsis (bacterial endocarditis, HIV, viral hepatitis)

Drug toxicity (Ergots, cocaine, amphetamines, others *)

Paraneoplastic syndromes

Atrial myxoma

Cholesterol emboli syndromes

* Not only mimics but can cause secondary vasculitis!

Objective 4 – To prove the diagnosis of vasculitis

I. Laboratory tests that are helpful in the diagnosis of vasculitis

  • Tests suggesting immune complex formation and/or deposition
  • RF and cryoglobulins
  • ANA
  • Low C3 or C4 levels
  • Tests suggesting necrotizing vasculitis without immunocomplex formation
  • ANCA
  • Test suggesting systemic inflammation
  • ESR
  • CRF

ANCA

  • ANCA by immunofluoresence
  • C-ANCA – Wegeners (60-90%)
  • P-ANCA – Microscopic polyangitis (50-80%)
  • Ulcerative colitis (40-80%)
  • Crohn’s (10-40%)
  • ANCA cytoplasmic antibodies
  • Proteinase 3 (PR3) = Wegener’s
  • Myeloperoxidose (MPA) – microscopic polyangitis
  • Other non-specific or not identified P-ANCA

II. Considerations on the diagnosis and classification of systemic vasculitis

  • Size of blood vessel
  • Epidemiologic features (age, sex, ethnic background)
  • Giant cell arteritis: Age>50, female 3:1, Northern European
  • Takayasu’s: Age<40, female 9:1, Asian
  • Behcet’s: Silk route countries
  • Polyarteritis: Males>females
  • Kawasaki’s: Children from Asian ancestry
  • Wegener’s: Caucasians>blacks
  • H-S purpura: Only 10% adults, 90% children
  • Pattern of organ involvement
  • Wegener’s: Kidney, upper airway, lung
  • H-S purpura: Kidney, GI tract, skin

  • Pathologic features
  • Granulomatous inflammation: giant cell, Takayasu, Wegener’s, Churg-Strauss, primary CNS
  • Pauci-immune versus IC deposition:
  • Wegener’s, MPA, CS (many are ANCA+) versus Goodpasture’s, HS, cryoglobulinemia, Bechet’s, hypersensitivity, secondary vasculitis
  • Infection Association: HBV with PN, HCV with Cryoglobulins

III. Role of Biopsy in Diagnosis

  • If biopsy impractical (large vessel, abdominal, etc) Angiograph (better than MRA)
  • Asymptomaticsite – low yield (>20%)
  • Symptomatic or abnormal sites (>65%)

Objective 5 – To learn the criteria for the diagnosis of systemic vasculitis

Names and Definitions of Vasculitis from the Chapel Hill Consensus Conference

I. Large-Vessel Vasculitis

Giant-cell (temporal)Granulomatous arteritis of the aorta and its major branches,

arteries with a predilection for the extacranial branches of the carotid artery. Often involves the temporal artery. Usually occurs in patients more than 50 year old and is often associated with polymyalgia rheumatica.

Takayasu’s arteritisGranulomatous inflammation of the aorta and its major branches. Usually occurs in patients younger than 50.

II. Medium-sized Vessel Vasculitis

Polyarteritis nodosaNecrotizing inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules.

Kawasaki’s diseaseArteritis involving large, medium-sized, and small arteries and associated with mucocutaneous lymph node syndrome. Coronary arteries are often involved. Aorta and veins may be involved. Usually occurs in children.

III. Small Vessel Vasculitis

Wegener’sGranulomatous inflammation involving the respiratory tract

Granulomatosis†and necrotizing vasculitis affecting small-to-medium-sized vessels (e.g., capillaries, venules, arterioles, and arteries). Necrotizing glomerulonephritis is common.

Churg-Strauss syndrome†Eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels and associated with asthma and eosinophilia.

Microscopic polyangiitis†Necrotizing vasculitis with few or no immune deposits affecting small vessels (capillaries, venules, or arterioles). Necrotizing arteritis involving small and medium-sized arteries may be present. Necrotizing glomerulonephritis is very common. Pulmonary capillaritis often occurs.

Henoch-SchönleinVasculitis with IgA-dominate immune deposits affecting

Purpura: small vessels (capillaries, venules, or arterioles). Typically involves skin, gut, and glomeruli and is associated with arthralgias or arthritis.

Essential CryoglobulinemicVasculitis with cryoglobulin immune deposits affecting Angiitis: small vessels (capillaries, venules, or arterioles) and

associated with cryoglobulins in serum. Skin and glomeruli are often involved.

†These vasculitides are associated with antineutrophil cytoplasmic auto-antibodies (ANCA).

Post Module Evaluation

Please place completed evaluation in an interdepartmental mail envelope and address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111).

1) Topic of module:______

2) On a scale of 1-5, how effective was this module for learning this topic? ______

(1= not effective at all, 5 = extremely effective)

3) Were there any obvious errors, confusing data, or omissions? Please list/comment below:

______

4) Was the attending involved in the teaching of this module? Yes/no (please circle).

5) Please provide any further comments/feedback about this module, or the inpatient curriculum in general:

6) Please circle one:

Attending Resident (R2/R3)Intern Medical student

1